Farm animals have long been used to nurture our bodies, but what if they could also help fight human diseases?

While most farmers will breed animals for desirable traits and veer away from animals known to have deficiencies, that’s not the case at Windswept Farms in Hopkins. Owners Mike and Heather Ludlam are breeding sheep to have a genetic defect and are garnering a premium price to do so. The defect causes sheep to produce an abundance of GM1 ganglioside, which is a substance that has been proven effective in treating Huntington’s disease, as well as other neurological disorders such as Parkinson’s and Alzheimer’s in humans.

DEVOTED: Mike and Heather Ludlam are committed to raising lambs for research. They hope the lambs will provide the link needed to find a cure for Huntington’s disease, which killed Mike’s sister in 2012.

What is causing the affected sheep to fall ill is a substance that humans with Huntington’s lack. GM1 ganglioside is a chemical that is found in the brain and is a normal part of the outer covering or membrane of nerve cells. It helps protect the brain and keeps cells healthy. By harvesting the substance, GM1 ganglioside, from the sheep and delivering it by either injection or inhalation, research has found it to restore normal motor behavior in mice afflicted with Huntington’s.

The research is not new, GMI ganglioside sourced from cow brains had been used to treat Parkinson’s in the past. However, that effort halted with the outbreak of mad cow disease and the fears that followed.

Larry Holler, a South Dakota veterinarian and farmer who researched the sheep disease, GM1 gangliosidosis, for his Ph.D. project, explains that all mammals produce GM1 glanglioside. “It’s a sugar with a fatty acid tail most prevalent in the brain, but is also in the spinal cord and other organs, but not in the muscle,” he says. Sheep with this disorder are overproducing the substance by about 40 times more than normal sheep, he adds, making them an excellent source of GM1.”

Holler has been a steward of advancing the research by raising and sourcing the affected sheep for almost 30 years.

Disease afflicts family
Huntington’s, a genetic disease, is dominate in humans, meaning those that inherit the trait, will eventually come down with the fatal disease. “It’s like a combination of Alzheimer’s, Parkinson’s and ALS all rolled into one,” Heather explains. Those with the disease may live perfectly normal lives as adolescents and young adults, but eventually the symptoms start to appear, she says. “It’s truly an awful disease.”

While affected sheep sold for research garner two to three times the going rate over non-affected sheep, the Ludlams also have a personal reason for raising the lambs.

Mike’s oldest sister, Dory, died of the disease in March 2012. Looking back, Mike says mental symptoms started in her early to mid-30s, although they really didn’t suspect the disease. Both Mike and Dory were adopted with no family medical history to reference. Mike, who is not a blood relative of Dory, says his training as a conservation officer (now retired) led him to believe she might be on drugs because of manic behavior. Those mental symptoms soon led to not being able to talk, walk, swallow or reason. She died at a care facility at age 51, but leaves behind three children, which have a 50% chance of developing the disease.

“Even though they now have a genetic test to see if you have the gene, with Dory, we didn’t know it was in the family,” Heather says. “And once they developed the genetic test, researchers thought it would eventually wipe out Huntington’s, but that hasn’t been the case, because many people don’t want to know and want to live as much of their lives as normal as possible.”

Holler, who calls Huntington’s disease the “nastiest disease around,” says about 30,000 people in the U.S. have clinical symptoms of the disease. “We are not sure how many are at risk — up to 100,000 or maybe higher,” he adds. “We estimate one lamb could treat one patient for one year.”

FOR A REASON: Shortly after moving to Hopkins, Heather Ludlam, a veterinarian, was given a lamb by a client. Over time Heather and her husband, Mike, expanded their flock with purebred Shetland and Targhee breeds, which the whole family showed. Now, their focus is on building a commercial flock that also produces lambs that produce GM1 gangliosidosis. The lambs garner a premium price and are used in research on neurological diseases in humans.

The Ludlams got involved after Mike read a small article in a trade publication about the effort to advance Huntington’s research by utilizing these unique sheep. They visited the Hollers, and even though the Ludlams were outside the area Holler likes to source the sheep, Holler says, “I had to include them — the Ludlams are special, tremendous supporters and friends.”

The Ludlams farm 50 acres, which includes 40 acres in pasture. When they first bought the place in 1993, Mike says he saw it as a place to hunt deer. The first week after moving in, Heather, a veterinarian, came home with a purebred Shetland lamb with a broken horn, given to her by a client. “She then said it needed a friend, which then lead to establishing a small flock of purebreds,” Mike says. They, along with all three of their children, have showed sheep in state and across the country.

Getting involved
The Ludlams had been transitioning to a commercial flock when they met the Hollers and felt compelled to get involved. They bought two carrier rams in 2015, and about 40 of their 100 ewes on the farm are carriers. Unlike humans, the genetic defect is recessive in lambs, meaning that for every 100 healthy carrier ewes bred to carrier rams,  about 25 will test positive for the disease, while 50 will carry the gene and the other 25 will be normal. Healthy ewe carriers join the breeding stock.

Heather says raising affected animals is no different than raising animals for commercial production. “The only extra step we have is a blood test — which we do not pay for — right at birth,” she says. “After weaning, the affected animals are shipped to the Hollers.”

The affected animals look and act the same as any other at birth, but at 3 to 4 months of age, they start to lack coordination and become “tipsy” as neurological functions deteriorate, Holler says. “They are separated from the rest of the flock to receive special care before they are slaughtered around 4.5 months. Their central nervous tissue is collected and sent off to a lab to be purified and sold for research.”

Currently, the carcass is not allowed to enter the commercial food chain; however, significant levels of GM1 ganglioside have not been detected in muscle tissue. That means it may gain approval in the future. In the meantime, if research continues to be favorable and production ramps up, there is discussion of establishing a pet food produced from the carcasses. A portion of the profits would then fund additional research.

Holler established GlycoScience Research Inc., which is the corporate structure or entity that works with all the participating sheep producers to help them with animal production. It coordinates the genetic tests that are used. There are 17 cooperator-producers in Michigan, North and South Dakota, Iowa, Minnesota, and Indiana. About 250 affected animals will be processed at the farm’s butchering facility this year, according to Holler.

Eventually, he sees the effort separated into regional groups, like a wagon wheel with the center being the collection point. “I can see Michigan as being a collection point at some time. There’s also interest in Oregon and Montana,” he says. “A producer in the state of New York that has 4,000 ewes has said, ‘Just give me the word.’” Holler says. “The interest is there, and there’s potential for a significant value-added opportunity for farmers. But we have to be careful not to let production outpace the science.”

Science moves slowly
GRI is working with Stephen Hersch at Harvard-Massachusetts General this summer with preclinical trials.

Funding is at the core of being able to move to clinical trials. It’s also the No. 1 stumbling block. “It’s challenging because we have a lot of moving parts in this project,” Holler says. “The traditional pharmaceutical companies don’t like the ag part of this project; they see it as being messy. And the venture capitalist folks who invest in projects are a little bit afraid of the scope of this project.”

While GM1 has also been proven effective for Parkinson’s, the U.S. research is focusing on Huntington’s because it is a rare disease and may qualify for an expedited approval process under the Orphan Drug Act of 1983.

Holler believes the affected sheep are the missing link in providing a safe, plentiful and sustainable natural source for ganglioside. “I’ve been living this journey. These lambs are a special creation of God,” he says. “Sometimes I wonder why I’ve been given this responsibility. We’ve hit some roadblocks, but bridges have been built — not as fast as we’d like, but we’ve had steady progress. This is really a value-added opportunity for producers, and production is not particularly difficult. It’s my goal to make a drug that is cost-effective, because you shouldn’t have to mortgage your life to stay alive.”

For the Ludlams, they believe that Heather coming home with a lamb right after moving to the farm was part of a grand plan.

For more information, visit glycoscienceresearch.com or visit Facebook. Holler can be reached at [email protected]